Summary for clan MA

Summary Structure Literature
Clan type peptidaseM04.001 - thermolysin (Bacillus thermoproteolyticus), MEROPS Accession MER0001026 (peptidase unit: 233-548); PDB accession 1TLP
HistoryBiochem.J. 290:205-218 (1993)
DescriptionWater nucleophile; water bound by single zinc ion ligated to two His (within the motif HEXXH) and Glu, His or Asp
Contents of clanClan MA contains a variety of metallopeptidases.
EvidenceThe families in clan MA are united by the presence of an HEXXH motif in which the two His residues are zinc ligands and the Glu has a catalytic function. The motif HEXXH occurs in non-peptidase proteins too, but a more specific motif can be defined for clan MA. This larger motif is Xaa-Xbb-Xcc-His-Glu-Xbb-Xbb-His-Xbb-Xdd in which Xaa is hydrophobic or Thr, Xbb is uncharged, Xcc is any amino acid except Pro, and Xdd is hydrophobic (Jongeneel et al., 1989). There is a third zinc ligand towards the C-terminus, and the nature of this varies with the subclan (see below).
Catalytic mechanismThe mechanism of catalysis by metallopeptidases in clan MA has been reviewed by Auld (2004).
Peptidase activityTypes of peptidase activity include aminopeptidase (in families M1, M61), carboxypeptidase (M2, M32), peptidyl-dipeptidase (M2), oligopeptidase (M3, M13) and endopeptidase (families M4, M10, M12 and others). The matrix metallopeptidases in family M10 and the ADAM peptidases and snake venom metallopeptidases in family M12 have been subjects of particularly intense research.
Protein foldThe molecule of snapalysin (M07.001) illustrates the minimal structure of the peptidase unit in clan MA. The snapalysin molecule contains a bundle of helices and a Greek key-like beta sheet, with the active site located between two helices (Kurisu et al., 1997). This general structure is common to all members of clan MA, but frequently a more elaborate second domain replaces the single helix that forms half of the active site in snapalysin; for example, in thermolysin (M04.001) the second domain is a bundle of five helices (Matthews et al., 1972). The molecules of most peptidases in clan MA contain non-peptidase domains as well as the peptidase unit.
Homologous non-peptidase familiesThe fold is largely confined to members of clan MA. A protein of unknown function from Aquifex aeolicus has a similar fold and may prove to represent a new family of metallopeptidases (Oganesyan et al., 2003).
Activation mechanismSome of the endopeptidases in subclan MA(E) are synthesised as proenzymes that are activated by removal of an N-terminal propeptide (e.g. pseudolysin, M04.005: Kessler & Safrin, 1994). The peptidases in subclan MA(M) are synthesised as inactive proenzymes. In some, the inactivity of the proenzyme is attributable to an interaction between a conserved Cys in the propeptide and the catalytic zinc ion that prevents the binding of a water molecule. This "cysteine switch" mechanism (Van Wart & Birkedal-Hansen, 1990) is found in families M8, M10 subfamily A, M11 and M12 subfamily B. Almost without exception, peptidases in subclan MA(M) that lack the cysteine switch contain a catalytically-important Tyr two residues beyond the Met of the Met-turn (see the Alignment for subclan MA(M)).
Other databases PFAMCL0126
SCOP55486

Families

Family Family Type Peptidase Structure
M06 immune inhibitor A peptidase ({Bacillus} sp.) (Bacillus thuringiensis) -
M07 snapalysin (Streptomyces lividans) Yes
M35 deuterolysin (Aspergillus flavus) Yes
M41 FtsH peptidase (Escherichia coli) Yes
M64 IgA peptidase ({Clostridium ramosum}-type) (Clostridium ramosum) -
M01 aminopeptidase N (Homo sapiens) Yes
M02 angiotensin-converting enzyme peptidase unit 1 (Homo sapiens) Yes
M03 thimet oligopeptidase (Rattus norvegicus) Yes
M04 thermolysin (Bacillus thermoproteolyticus) Yes
M05 mycolysin (Streptomyces cacaoi) -
M09 collagenase V ({Vibrio} spp.) (Vibrio alginolyticus) Yes
M100 spartan peptidase (Homo sapiens) -
M101 flagellinolysin (Clostridium haemolyticum) -
M102 DA1 peptidase ({Arabidopsis thaliana}) (Arabidopsis thaliana) -
M106 FP0506 g.p. ({Flavobacterium psychrophilum}) (Flavobacterium psychrophilum) -
M13 neprilysin (Homo sapiens) Yes
M26 IgA1-specific metallopeptidase (Streptococcus sanguinis) -
M27 tentoxilysin (Clostridium tetani) Yes
M30 hyicolysin (Staphylococcus hyicus) -
M32 carboxypeptidase Taq (Thermus aquaticus) Yes
M34 anthrax lethal factor (Bacillus anthracis) Yes
M36 fungalysin (Aspergillus fumigatus) -
M48 Ste24 peptidase (Saccharomyces cerevisiae) Yes
M49 dipeptidyl-peptidase III (Rattus norvegicus) Yes
M56 BlaR1 peptidase (Staphylococcus aureus) -
M60 enhancin (Lymantria dispar nucleopolyhedrovirus) -
M61 glycyl aminopeptidase (Sphingomonas capsulata) -
M76 Atp23 peptidase (animal-type) (Homo sapiens) -
M78 ImmA peptidase (Bacillus subtilis) -
M85 NleC peptidase ({Escherichia coli}) (Escherichia coli) -
M87 chloride channel accessory protein 1 (Homo sapiens) -
M88 IMPa peptidase ({Pseudomonas aeruginosa}) (Pseudomonas aeruginosa) -
M90 MtfA peptidase (Escherichia coli) Yes
M91 NleD peptidase ({Escherichia coli}-type) (Escherichia coli) -
M93 BACCAC_01431 g.p. ({Bacteroides caccae}) and similar (Bacteroides caccae) -
M95 abylysin ({Pyrococcus abyssi}) (Pyrococcus abyssi) -
M98 YghJ g.p. ({Escherichia coli}) (Escherichia coli) -
M08 leishmanolysin (Leishmania major) Yes
M10 matrix metallopeptidase-1 (Homo sapiens) Yes
M105 MAP1 peptidase ({Myxococcus xanthus}, {Pimelobacter} sp.) (Myxococcus xanthus) -
M11 gametolysin (Chlamydomonas reinhardtii) -
M12 astacin (Astacus astacus) Yes
M43 cytophagalysin (Cytophaga sp.) Yes
M54 archaelysin (Methanocaldococcus jannaschii) -
M57 prtB g.p. ({Myxococcus xanthus}) (Myxococcus xanthus) -
M66 StcE peptidase (Escherichia coli) -
M72 peptidyl-Asp metallopeptidase (Pseudomonas aeruginosa) -
M80 Wss1 peptidase ({Saccharomyces}-type) (Saccharomyces cerevisiae) -
M84 MpriBi peptidase ({Bacillus} sp.) (Bacillus intermedius) -
M97 EcxAB peptidase (Escherichia coli) -

Distribution of clan MA among Kingdoms of Organisms

FamilyBacteriaArchaeaProtozoaFungiPlantsAnimalsViruses
M1-------
M2-------
M3-------
M4-------
M5-------
M6-------
M7-------
M8-------
M9-------
M10-------
M10-------
M11-------
M12-------
M15-------
M16-------
M11-------
M12-------
M13-------
M26-------
M27-------
M30-------
M32-------
M34-------
M35-------
M36-------
M41-------
M43-------
M48-------
M49-------
M54-------
M56-------
M57-------
M60-------
M61-------
M64-------
M66-------
M72-------
M76-------
M78-------
M80-------
M84-------
M85-------
M87-------
M88-------
M90-------
M91-------
M93-------
M95-------
M97-------
M98-------
Clan-------